Research Papers:

MiR-128 reverses the gefitinib resistance of the lung cancer stem cells by inhibiting the c-met/PI3K/AKT pathway

Jingjin Jiang, Xiaoning Feng, Wenjing Zhou, Yue Wu and Yunmei Yang _

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Oncotarget. 2016; 7:73188-73199. https://doi.org/10.18632/oncotarget.12283

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Jingjin Jiang1,*, Xiaoning Feng2,*, Wenjing Zhou1, Yue Wu1, Yunmei Yang1

1Department of geriatrics, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China

2Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China

*These authors contributed equally to this work

Correspondence to:

Yunmei Yang, email: [email protected]

Keywords: PC9-CSCs, miR-128, gefitinib, c-met, PI3K/AKT

Received: July 06, 2016     Accepted: September 21, 2016     Published: September 27, 2016


Gefitinib is a first line anti-tumor drug used for the treatment of patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations. However, the drug resistance to gefitinib limits its clinical application. Here, we observed the CSCs of PC9 are obviously resistant to gefitinib compared with the non-CSCs. Furthermore, we found the gefitinib failed to suppress the PI3K/AKT pathway in the PC9-CSCs. Mechanically, we showed significant down-regulation of miR-128 in the PC9-CSCs compared with the non-CSCs. Overexpression of miR-128 significantly increased the sensitivity of PC9-CSCs to gefitinib-induced apoptosis. In addition, the gene of c-met was proved to be directly inhibited by miR-128. Enforced expression of c-met could “rescue” the miR-128 promoted apoptosis and cleavage of caspases in PC9-CSCs treated with gefitinib. Thus, these results indicate that the miR-128/c-met pathway enhances the gefitinib sensitivity of the lung cancer stem cells by suppressing the PI3K/AKT pathway.

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